ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.2047C>T (p.Arg683Ter) (rs121917904)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000333649 SCV000362900 likely pathogenic ERCC6-Related Disorders 2017-07-24 criteria provided, single submitter clinical testing The ERCC6 c.2047C>T (p.Arg683Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The p.Arg683Ter variant been reported in two studies in which it is found in two patients including one homozygote with cerebrooculofacioskeletal syndrome (CFSS) and one compound heterozygote with Cockayne syndrome (Laugel et al. 2008; Calmels et al. 2016). Control data are not available for the p.Arg683Ter variant which is reported at a frequency of 0.00005 in the European (non-Finnish) population of the Exome Aggregation Consortium. Western blot analysis demonstrated that the variant resulted in an absence of protein. Complementation assays in CFSS patient fibroblasts transfected with wild type ERCC6 demonstrated rescue of DNA repair deficiency (Laugel et al. 2008). Although the p.Arg683Ter variant is described in the literature in association with autosomal recessive inheritance, an increased risk for macular degeneration due to heterozygous variants may exist. Due to the potential impact of stop-gained variants and evidence from the literature, the p.Arg683Ter variant is classified as likely pathogenic for ERCC6-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000001781 SCV000021937 pathogenic Cerebrooculofacioskeletal syndrome 1 2008-09-01 no assertion criteria provided literature only
Counsyl RCV000983998 SCV000788972 pathogenic DE SANCTIS-CACCHIONE SYNDROME 2017-01-13 no assertion criteria provided clinical testing

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